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NEW YORK (Reuters Health) - The incidence of non-Hodgkin lymphoma (NHL) remains high in HIV-infected patients despite treatment with antiretroviral therapy, and ongoing low-level HIV replication may be a contributing factor, new research hints.

"In patients successfully treated with ART, any HIV viremia, including lower levels previously thought to be inconsequential, potentially puts them at risk for diseases with significant morbidity and mortality such as non-Hodgkin lymphoma," Dr. Chad Achenbach of the Center for Global Health at Northwestern University in Chicago, Illinois, told Reuters Health by email.

"Earlier initiation of potent ART and maximal continuous suppression of HIV viremia may further reduce NHL risk," he and his colleagues conclude in Clinical Infectious Diseases online February 12.

While the incidence of NHL, an AIDS-defining condition, has fallen in the modern era of ART, rates continue to be four to 23 times higher in HIV-infected patients relative to uninfected adults, they point out. They hypothesized that "any detectable HIV viremia is a driver of immune dysfunction, B cell activation, and higher subsequent risk for NHL."

A study of HIV-infected patients followed in the Center for AIDS Research Network of Integrated Clinical Systems supports their hypothesis.

They found a "high" overall incidence of NHL (171 per 100,000 person-years) in a large group of patients receiving effective ART. The incidence far exceeded that reported in HIV uninfected populations of approximately 10 to 20 per 100,000 person-years.

"A high incidence of NHL was noted even among patients with nadir CD4 cell count > 200 cells/l (140 per 100,000 PY) suggesting this cancer is associated with HIV infection above and beyond the level of immunodeficiency categorized as 'AIDS-defining' by the CDC in 1993," the investigators say.

After adjusting for the known confounders of older age, white race, male sex, HCV co-infection, and time-varying CD4 cell count, NHL risk was higher when HIV viremia was above the limit of detection (50 copies/mL) in a dose-dependent manner, they say, although the results were "imprecise" due to the relatively small number of NHL cases (n=37).

Why do NHL rates remain high in the era of effective ART? "It's a combination of factors," Dr. Achenbach told Reuters Health, "including aging, chronic immune dysfunction, inflammation, and B cell activation potentially driven by viremia from ART interruptions, cryptic HIV replication or herpes virus reactivation. Also, patients who are unaware of their infection continue to present late with AIDS defining disease such as NHL before getting on ART." he said.

Current U.S. HIV treatment guidelines call for starting ART and maximum virologic suppression in nearly all infected patients, regardless of CD4 cell count, to reduce transmission and clinical events and to maximize life expectancy, the investigators note in their article. They write, "Our study supports these recommendations and further contributes to mounting evidence that HIV replication, even at low levels, is associated with increased morbidity and mortality."

"Moving forward, studies should include NHL as an important clinical endpoint along with non-AIDS defining cancers," the investigators conclude.